USON, VERONICA M.

4:30-6:00 TTH

APREPITANT

Description:

Aprepitant, an antiemetic, is a substance P/neurokinin 1 (NK1) receptor antagonist which, in

combination with other antiemetic agents, is indicated for the prevention of acute and delayed
nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer
chemotherapy. Aprepitant is a selective high-affinity antagonist of human substance
P/neurokinin 1 (NK1) receptors. Aprepitant has little or no affinity for serotonin (5-HT3),
dopamine, and corticosteroid receptors, the targets of existing therapies for chemotherapy-
induced nausea and vomiting (CI NV).

Synonyms:

 3-(((2R,3S)-3-(P-Fluorophenyl)-2-(((alphar)-alpha-methyl-3,5-
bis(trifluoromethyl)benzyl)oxy)morpholino)methyl)-delta(2)-1,2,4-triazolin-5-one

 Aprepitant

 Aprépitant

 Aprepitantum

Chemical Formula: C23H21F7N4O3

IUPAC Name: 3-{[(2R,3S)-2-[(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]-3-(4-

fluorophenyl)morpholin-4-yl]methyl}-4,5-dihydro-1H-1,2,4-triazol-5-one

Indication:

For the prevention of nausea and vomiting associated with highly emetogenic cancer
chemotherapy, including high-dose cisplatin (in combination with other antiemetic agents).

Associated Conditions:

 Nausea and vomiting

Pharmacodynamics:

Aprepitant, an antiemetic, is a substance P/neurokinin 1 (NK1) receptor antagonist which, in

combination with other antiemetic agents, is indicated for the prevention of acute and delayed
nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer
chemotherapy. Aprepitant is a selective high-affinity antagonist of human substance
P/neurokinin 1 (NK1) receptors. Aprepitant has little or no affinity for serotonin (5-HT3),
dopamine, and corticosteroid receptors, the targets of existing therapies for chemotherapy-
induced nausea and vomiting (CI NV).

Mechanism of action:

Aprepitant has been shown in animal models to inhibit emesis induced by cytotoxic
chemotherapeutic agents, such as cisplatin, via central actions. Animal and human Positron
Emission Tomography (PET) studies with Aprepitant have shown that it crosses the blood brain
barrier and occupies brain NK1 receptors. Animal and human studies show that Aprepitant
augments the antiemetic activity of the 5-HT3-receptor antagonist ondansetron and the
corticosteroid ethasone and inhibits both the acute and delayed phases of cisplatin induced
emesis.

Absorption: The mean absolute oral bioavailability of aprepitant is approximately 60 to 65%.

Volume of distribution: 70 L

Protein binding: >95%

Metabolism: Aprepitant is metabolized primarily by CYP3A4 with minor metabolism by CYP1A2

and CYP2C19. Seven metabolites of aprepitant, which are only weakly active, have been
identified in human plasma.

Route of elimination: Aprepitant is eliminated primarily by metabolism; aprepitant is not renally

excreted. Aprepitant is excreted in the milk of rats. It is not known whether this drug is excreted
in human milk.

Half-life: 9-13 hours

Clearance: Apparent plasma cl=62-90 mL/min

Toxicity: Asthenia, hiccups

Food Interactions: Take without regard to meals.